Archaeal genes code for GGDEF domain proteins with diguanylate cyclase activity

This is a Preprint and has not been peer reviewed. This is version 1 of this Preprint. You must log in to post a comment. There are no comments or no comments have been made public for this article. This is a Preprint and has not been peer reviewed. This is version 1 of this Preprint. Add a Comment You must log in to post a comment. Comments There are no comments or no comments have been made public for this article. A biofilm-like tightly surface-associated mode of growth of pre-cellular life protected by an extracellular matrix has been hypothesized to be a prerequisite for the emergence of cellular life and its persistence under challenging environmental conditions. Ubiquitous in Bacteria including members of the deepest branching phyla, cyclic di-GMP, a positive regulator of biofilm formation, has not yet been detected in Archaea. Thus, whether cyclic di-GMP has been present as a primordial biofilm activator in the last universal common ancestor (LUCA) of Bacteria and Archaea remains unanswered. In this work bioinformatic analysis and structural modelling identified GGDEF domain proteins present in distinct archaeal isolates and metagenome associated genomes of confirmed archaeal origin. In particular, phenotypic and in vivo assays in combination with catalytic mutants in the heterologous Salmonella system indicated that the complex Rec-PAS/PAC-PocR-GGDEF-HD-GYP domain protein of Methanocella arvoryzae MRE50, a member of the Stenosarchaea order Methanocellales and other archaeal GGDEF domain proteins, possess diguanylate cyclase activity. While cyclic di-GMP signaling is ubiquitous in Bacteria, it can also rapidly disappear in evolution. Thus, it remains to be answered whether cyclic di-GMP signaling has been actively depleted from archaeal isolates with few synthesis genes to be sporadically maintained, whether cyclic di-GMP signaling has been secondarily introduced by horizontal gene transfer into Archaea or whether both scenarios have concomitantly occurred. https://doi.org/10.32942/X2KH36 Life Sciences Biofilm, origin of life, cyclic di-GMP Published: 2026-04-08 00:53 Last Updated: 2026-04-08 00:53 CC BY Attribution 4.0 International Conflict of interest statement: None Data and Code Availability Statement: Not applicable Language: English